Evidence map›Paper›PMID 36823301›Full record

ArticleNature medicine2023

Gut microbial metabolism of 5-ASA diminishes its clinical efficacy in inflammatory bowel disease.

Raaj S Mehta, Jared R Mayers, Yancong Zhang, Amrisha Bhosle, Nathaniel R Glasser, Long H Nguyen, Wenjie Ma, Sena Bae, Tobyn Branck, Kijun Song and 10 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
21.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Gut microbes · 2026
    Article
  4. Review
  5. Pharmacomicrobiomics-driven targeted drug delivery for precision microbiome modulation.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
    Review
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  7. Review
  8. Review
  9. Article
  10. Review
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  17. Review
  18. Article
  19. Article
  20. Targeted intestinal barrier repairActa pharmaceutica Sinica. B · 2026
    Article

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 1 country.

Raaj S Mehta *Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jared R Mayers *Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8607-1787
Yancong ZhangBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2768-2975
Amrisha BhosleBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nathaniel R GlasserResnick Sustainability Institute, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-2833-5166
Long H NguyenDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5436-4219
Wenjie MaDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Sena BaeDepartment of Immunology & Infectious Disease, T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Tobyn BranckBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Kijun SongDepartment of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6037-9345
Luke SebastianDepartment of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Julian Avila PachecoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9388-3946
Hyuk-Soo SeoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0646-2102
Clary ClishBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8259-9245
Sirano Dhe-PaganonDepartment of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0824-5929
Ashwin N AnanthakrishnanDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Eric A FranzosaBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8798-7068
Emily P BalskusBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5985-5714
Andrew T ChanDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Curtis HuttenhowerBroad Institute of MIT and Harvard, Cambridge, MA, USA. chuttenh@hsph.harvard.edu.ORCID http://orcid.org/0000-0002-1110-0096
Broad Institute · USHarvard University · USBrigham and Women's Hospital · USCalifornia Institute of Technology · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
RESPIRATORY RESEARCHT32HL007633 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI George R Washko · 1985 to 2026
$14.9M
A comprehensive platform for novel therapy development from the microbiomeR24DK110499 · NIDDK · BROAD INSTITUTE, INC. · PI HUTTENHOWER, CURTIS · 2017 to 2021
$7.7M
Precision Prevention Research ProgramR35CA253185 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Andrew T Chan · 2020 to 2026
$6.9M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Dietary strategies for rational manipulation of the gut microbiome in inflammatory bowel diseaseK23DK125838 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI NGUYEN, LONG H · 2020 to 2024
$1.0M
NCI NIH HHS R35 CA253185NIDDK NIH HHS K23 DK125838NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R24 DK110499NIGMS NIH HHS P30 GM124165NIH HHS S10 OD021527
6 · The paper itself

Abstract

For decades, variability in clinical efficacy of the widely used inflammatory bowel disease (IBD) drug 5-aminosalicylic acid (5-ASA) has been attributed, in part, to its acetylation and inactivation by gut microbes. Identification of the responsible microbes and enzyme(s), however, has proved elusive. To uncover the source of this metabolism, we developed a multi-omics workflow combining gut microbiome metagenomics, metatranscriptomics and metabolomics from the longitudinal IBDMDB cohort of 132 controls and patients with IBD. This associated 12 previously uncharacterized microbial acetyltransferases with 5-ASA inactivation, belonging to two protein superfamilies: thiolases and acyl-CoA N-acyltransferases. In vitro characterization of representatives from both families confirmed the ability of these enzymes to acetylate 5-ASA. A cross-sectional analysis within the discovery cohort and subsequent prospective validation within the independent SPARC IBD cohort (n = 208) found three of these microbial thiolases and one acyl-CoA N-acyltransferase to be epidemiologically associated with an increased risk of treatment failure among 5-ASA users. Together, these data address a longstanding challenge in IBD management, outline a method for the discovery of previously uncharacterized gut microbial activities and advance the possibility of microbiome-based personalized medicine.

Indexed as

Gastrointestinal MicrobiomeInflammatory Bowel DiseasesCross-Sectional StudiesHumansMesalamineTreatment OutcomeMesalamine

Identifiers

PMID36823301
PMCPMC10928503
OpenAlexW4321611584

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.